More than 1 million cases of clinically recognized pelvic inflammatory disease occur in American women each year. In addition, recent studies suggest that even larger numbers of women develop clinically unrecognized endometrial and tubal infection that has been termed "silent salpingitis". Sexually transmitted pathogens, principally Chlamydia trachomatis, Neisseria gonorrhoeae, and the anaerobes associated with bacterial vaginosis play an etiologic role in most of these cases. Serious sequellae of these upper genital tract infections, principally infertility, ectopic pregnancy and chronic pelvic pain have increased dramatically in prevalence in recent years. The majority of these cases occur in young women, many belonging to minority racial groups. This program project grant proposes multidisciplinary studies focused upon improving our understanding of the epidemiology, microbial etiology, clinical presentation, pathogenesis, and prevention of both clinically apparent and inapparent upper genital tract infection. Four interrelated projects are proposed. Project 1 will evaluate acute pelvic inflammatory disease and resultant tubal infertility in Nairobi, Kenya, determining the impact of HIV infection on the risk, microbial etiology, severity and response to therapy in women with laparoscopically verified PID and defining both behavioral and biological risk factors for PID in this setting. The project will also evaluate a World Health Organization algorithm for the clinical diagnosis of PID. Project 2 will define the microbial etiology, epidemiology, histopathology, and response to treatment of chronic endometrial infection, the prelude to silent salpingitis. Project 3 will utilize a primate model of salpingitis and infertility to evaluate the impact of specific antimicrobial and anti- inflammatory therapy upon tubal scarring, and to study the pathogenesis of tubal scarring. The project will provide information important to the design of subsequent human treatment trials. Project 4 will utilize molecular techniques to study the persistence of chlamydial infection in endometrial and tubal tissues obtained from patients with acute and chronic infection, infertility, and ectopic pregnancy. The project will also evaluate the presence of the 57kDa antigen in infected tissues and the serological response to this antigen in relevant patient groups. Four cores, including a chlamydial and gonococcal laboratory core, an administrative unit, a biostatistical core, and a behavioral sciences core will interact with the various projects. The behavioral core will facilitate the collection and analysis of meaningful behavioral data from all of the clinical projects. The information collected in these multidisciplinary, interrelated studies should eventually result in improved public health control of upper genital tract infections in women.